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The Possible “Proton Sponge ” Effect of Polyethylenimine (PEI) Does Not Include Change in Lysosomal pH

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TLDR
Measurements of lysosomal pH as a function of PEI content and correlate the results to the "proton sponge " hypothesis show that PEI does not induce change in lysoomic pH as previously suggested and quantification ofPEI concentrations inLysosomes makes it uncertain that the " proton sponge ' effect is the dominant mechanism of polyplex escape.
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This article is published in Molecular Therapy.The article was published on 2013-01-01 and is currently open access. It has received 616 citations till now. The article focuses on the topics: Polyethylenimine.

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Citations
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Degradable lipid nanoparticles with predictable in vivo siRNA delivery activity.

TL;DR: It is shown that lipidoid nanoparticles mediate potent gene knockdown in hepatocytes and immune cell populations upon IV administration to mice (siRNA EC50 values as low as 0.01 mg/kg); new design criteria that reliably predict in vivo siRNA delivery efficacy without any prior biological testing are described.
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Gold Nanoparticles for Nucleic Acid Delivery

TL;DR: This review focuses on the use of covalent and noncovalent gold nanoparticle conjugates for applications in gene delivery and RNA-interference technologies and challenges in nucleic acid delivery, including endosomal entrapment/escape and active delivery/presentation of nucleic acids in the cell.
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Overcoming Nonviral Gene Delivery Barriers: Perspective and Future

TL;DR: This work presents the existing delivery barriers and summarize current vector-specific strategies to overcome said barriers, and focuses on the gene delivery barriers associated with the two most common classes of nonviral vectors, cationic-based lipids and polymers.
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The Endosomal Escape of Nanoparticles: Toward More Efficient Cellular Delivery

TL;DR: This Topical Review highlights the current understanding of the mechanisms by which nanoparticles escape the endosome, and the emerging techniques to improve the quantification of endosomal escape.
References
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Journal ArticleDOI

A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine

TL;DR: Together, these properties make PEI a promising vector for gene therapy and an outstanding core for the design of more sophisticated devices because its efficiency relies on extensive lysosome buffering that protects DNA from nuclease degradation, and consequent lysOSomal swelling and rupture that provide an escape mechanism for the PEI/DNA particles.
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Understanding biophysicochemical interactions at the nano–bio interface

TL;DR: Probing the various interfaces of nanoparticle/biological interfaces allows the development of predictive relationships between structure and activity that are determined by nanomaterial properties such as size, shape, surface chemistry, roughness and surface coatings.
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Nonviral Vectors for Gene Delivery

TL;DR: Two nonviral gene delivery systems using either biodegradable poly(D,Llactide-co-glycolide) (PLG) nanoparticles or cell penetrating peptide (CPP) complexes have been designed and studied using A549 human lung epithelial cells.
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Exploring polyethylenimine-mediated DNA transfection and the proton sponge hypothesis.

TL;DR: The relatively high transfection efficiency of polyethylenimine vectors has been hypothesized to be due to their ability to avoid trafficking to degradative lysosomes, and according to the proton sponge hypothesis, the buffering capacity of PEI leads to osmotic swelling and rupture of endosome, resulting in the release of the vector into the cytoplasm.
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Chloride Accumulation and Swelling in Endosomes Enhances DNA Transfer by Polyamine-DNA Polyplexes

TL;DR: The results provide direct support for the proton sponge hypothesis and thus a rational basis for the design of improved non-viral vectors for gene delivery.
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